本文選題：可溶性CD14　切入點(diǎn)：Toll樣受體4　出處：《第一軍醫(yī)大學(xué)》2006年博士論文　論文類型：學(xué)位論文

【摘要】：在移植免疫中，T淋巴細(xì)胞在雙信號(hào)刺激下才能被激活和發(fā)生增殖，從而啟動(dòng)由淋巴細(xì)胞、細(xì)胞因子、補(bǔ)體等參予的錯(cuò)綜復(fù)雜的移植排斥反應(yīng)。如果抗原提呈細(xì)胞(antigen present cell，APC)只提供MHC-抗原肽復(fù)合物而不提供CD80、CD86等共刺激信號(hào)，將使淋巴細(xì)胞無能，誘導(dǎo)免疫耐受。 目前，國內(nèi)、外關(guān)于移植免疫的研究主要集中在以T／B淋巴細(xì)胞及其下游細(xì)胞因子為中心的免疫過程，由于T／B淋巴細(xì)胞活化后移植免疫網(wǎng)絡(luò)的復(fù)雜性，以該免疫網(wǎng)絡(luò)某一個(gè)環(huán)節(jié)為靶點(diǎn)的治療措施往往事倍功半。 顯然，針對(duì)淋巴細(xì)胞活化的上游信號(hào)傳導(dǎo)者APC的研究將具有顯而易見的優(yōu)勢(shì)。APC表面共刺激分子的表達(dá)是決定T細(xì)胞異基因免疫反應(yīng)性的關(guān)鍵因素。APC表面CD80、CD86等共刺激分子的下調(diào)可以使APC轉(zhuǎn)變?yōu)橹履褪苄约?xì)胞，使T細(xì)胞失去發(fā)生異基因反應(yīng)的能力。 但問題是，CD80、CD86的表達(dá)是由誰調(diào)控的?如何調(diào)控的?1997年，人類天然免疫模式識(shí)別受體TOLL樣受體(Toll like receptor，TLR)的發(fā)現(xiàn)使得以APC為主要對(duì)象的移植免疫研究成為可能。早期關(guān)于TLR的研究主要集中在抗感染免疫方面，TLR是天然免疫用以識(shí)別各種致病微生物共有結(jié)構(gòu)的“工具”，TLR與各種致病微生物共有的保守結(jié)構(gòu)也即病原相關(guān)分子模式結(jié)合后，激活相應(yīng)的信號(hào)傳導(dǎo)通路，促進(jìn)單核／巨噬細(xì)胞、樹突狀細(xì)胞等抗原提呈細(xì)胞的成熟與活化，上調(diào)CD80、CD86等共刺激分子的表達(dá)，啟動(dòng)天然免疫，消滅入侵的病原體。隨著研究的進(jìn)一步深入，發(fā)現(xiàn)TLR還在移植免疫、動(dòng)脈粥樣硬化形成中起重要作用。其中，TLR4與移植免疫關(guān)系的研究顯示出極具誘人的前景。 在可溶性CD14(soluble CD14，sCD14)幫助下，APC上的TLR4與革蘭氏陰性菌內(nèi)毒素脂多糖LPS結(jié)合并活化，通過一系列信號(hào)傳導(dǎo)，，引起NF-κB活化，
[Abstract]:In transplant immunity, T lymphocytes can only be activated and proliferated under the stimulation of double signals, and thus activated by lymphocytes, cytokines, If antigen presenting cell antigen present cell (APC) provides only MHC-antigen peptide complex but not costimulatory signal such as CD80 or CD86, it will cause lymphocyte anergy and induce immune tolerance. At present, domestic and foreign researches on transplantation immunity mainly focus on the immune process centered on T / B lymphocytes and their downstream cytokines. Because of the complexity of the transplantation immune network after T / B lymphocytes are activated, Therapeutic measures targeted at one link of the immune network are often half-effective. Obviously, The study on upstream signal transducers of lymphocyte activation will have obvious advantages. The expression of costimulatory molecules on APC surface is the key factor to determine the allogeneic immunoreactivity of T cells. CD80 CD86 and other costimulatory molecules on the surface of APC are the key factors to determine the allogenic immunoreactivity of T cells. The down-regulation of APC can transform APC into tolerant cells. Make T cells lose the ability to produce allogenic reactions. But the question is, who regulates the expression of CD80? How? 1997, The discovery of human innate immune pattern recognition receptor TOLL-like receptor Toll like receptor makes it possible to study transplantation immunity with APC as the main object. Early studies on TLR mainly focused on anti-infection immunity. In order to identify the common structures of various pathogenic microorganisms, the TLR binds to the conserved structure shared by various pathogenic microorganisms, that is, pathogen-related molecular patterns. Activating the corresponding signal transduction pathway, promoting the maturation and activation of antigen-presenting cells such as monocytes / macrophages and dendritic cells, upregulating the expression of costimulatory molecules such as CD80, CD86, and initiating innate immunity. With the further development of research, it is found that TLR still plays an important role in the pathogenesis of atherosclerosis, and the relationship between TLR4 and transplantation immunity is very attractive. Under the help of soluble CD14(soluble CD14s CD14, TLR4 on APC binds and activates lipopolysaccharide (LPS) from gram-negative bacteria, which activates NF- 魏 B through a series of signal transduction.
【學(xué)位授予單位】：第一軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R699.2;R392.4

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